The object of this research program is to carry out biophysical and biochemical studies on the nucleic acids in order to provide insight concerning the mechanism of their action in biological systems. A central part of this program is to use the information on the recently determined three-dimensional structure of transfer RNA in order to understand more fully its mode of action in biological systems. One way of obtaining this information is to determine the three-dimensional structure of proteins which interact with transfer RNA. X-ray diffraction techniques will be used to solve the structure of these macromolecules. In addition, attempts will be made to co-crystallize transfer RNA with proteins with which it interacts. The molecular structure of these complexes will be determined and they should provide significant insight into the manner in which proteins recognize nucleic acids. Crystallographic studies will also be carried out on other nucleic acid components, including oligonucleotides, in order to study their natural conformation as well as the manner in which their conformation is modified by interaction with mutagens or carcinogens. This includes the structure of DNA fragment of defined sequence. Another part of this research project is related to the mechanism of action of nucleic acids in protein synthesis. Studies will be carried out on specificity of tRNA aminoacyl synthetases as well as the manner in which tRNA is involved in codon-anticodon interactions.